The objective of this project is the effective use of biochemical and cellular assays of human tissue and body fluid specimens in epidemiologic studies seeking evidence of adverse effects associated with specific environmental exposures. It emphasizes interdisciplinary development of ideas and methodologies coupled with attention to details of both the laboratory procedures and the gathering and analysis of data concerning human subjects. Current effort focuses on the development of techniques for identifying genetic damage and alterations in metabolism associated with human exposure to potentially toxic substances. These techniques are being used in model studies of individuals exposed to known amounts of carcinogenic and mutagenic agents used for cancer chemotherapy, occupational groups, smokers, and individuals accidentally exposed to large quantities of PCBs. These studies are designed to help evaluate and refine assay and clinical methods, to investigate mechanisms involved in specific models of human desease, and to investigate the effects of exposures that may be important to public health.